American Family Physician

N onsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat inflammation, pain, and fever by decreasing prostaglandin synthesis through blockage of the cyclooxygenase (COX) enzyme. Table 1 lists NSAID dosages and monthly costs. There is little evidence to support differences in effectiveness for pain treatment when comparing all NSAIDs. Aspirin is used for primary and secondary prevention of coronary artery disease, stroke, and some colorectal cancers. The two major isoforms of COX (COX-1 and COX-2) are inhibited by nonselective NSAIDs. COX-2 is also inhibited by selective NSAIDs. All nonselective NSAIDs inhibit platelet aggregation through inhibition of COX-1 and the thromboxane A 2 (TXA 2 ) pathway. Aspirin is unique in this regard because it binds covalently and irreversibly to the COX enzyme responsible for mediating platelet aggregation, and its action lasts for the lifetime of the platelet (eight to 12 days). COX-2 inhibitors have minimal antiplatelet effects because they do not affect the TXA 2 pathway. Because prostaglandin-mediated gastroprotection occurs through the COX-1 enzyme, COX-2 inhibitors were designed with the goal of decreasing gastrointestinal (GI) complications. NSAIDs are associated with morbidity related to many different body systems: GI, cardiovascular, hepatic, renal, hematologic, central nervous, and respiratory. There are also special considerations for children and pregnant or lactating women. Adverse effects from NSAIDs can occur at any time while taking them (Table 2); however, there is some evidence to support increased incidence of adverse effects with increased duration and dosing of selective and nonselective NSAIDs. Research has not shown whether Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used, but have risks associated with their use, including significant upper gastrointestinal tract bleeding. Older persons, persons taking anticoagulants, and persons with a history of upper gastrointestinal tract bleeding associated with NSAIDs are at especially high risk. Although aspirin is cardioprotective, other NSAIDs can worsen congestive heart failure, can increase blood pressure, and are related to adverse cardiovascular events, such as myocardial infarction and ischemia. Cyclooxygenase-2 inhibitors have been associated with increased risk of myocardial infarction; however, the only cyclooxygenase-2 inhibitor still available in the United States, celecoxib, seems to be safer in this regard. Hepatic damage from NSAIDs is rare, but these medications should not be used in persons with cirrhotic liver diseases because bleeding problems and renal failure are more likely. Care should be used when prescribing NSAIDs in persons taking anticoagulants and in those with platelet dysfunction, as well as immediately before surgery. Potential central nervous system effects include aseptic meningitis, psychosis, and tinnitus. Asthma may be induced or exacerbated by NSAIDs. Although most NSAIDs are likely safe in pregnancy, they should be avoided in the last six to eight weeks of pregnancy to prevent prolonged gestation from inhibition of prostaglandin synthesis, premature closure of the ductus arteriosus, and maternal and fetal complications from antiplatelet activity. Ibuprofen, indomethacin, and naproxen are safe in breastfeeding women. Care should be taken to prevent accidental NSAID overdose in children by educating parents about correct dosing and storage in childproof containers. (Am Fam Physician. 2009;80(12):1371-1378. Copyright © 2009 American Academy of Family Physicians.)